Molecular Genetics, Technical University Darmstadt, 64287 Darmstadt, Germany.
Nucleic Acids Res. 2022 Jun 10;50(10):5818-5833. doi: 10.1093/nar/gkac357.
The assembly of high molecular mass ribonucleoprotein complexes typically relies on the binary interaction of defined RNA sequences or precisely folded RNA motifs with dedicated RNA-binding domains on the protein side. Here we describe a new molecular recognition principle of RNA molecules by a high molecular mass protein complex. By chemically probing the solvent accessibility of mitochondrial pre-mRNAs when bound to the Trypanosoma brucei editosome, we identified multiple similar but non-identical RNA motifs as editosome contact sites. However, by treating the different motifs as mathematical graph objects we demonstrate that they fit a consensus 2D-graph consisting of 4 vertices (V) and 3 edges (E) with a Laplacian eigenvalue of 0.5477 (λ2). We establish that synthetic 4V(3E)-RNAs are sufficient to compete for the editosomal pre-mRNA binding site and that they inhibit RNA editing in vitro. Furthermore, we demonstrate that only two topological indices are necessary to predict the binding of any RNA motif to the editosome with a high level of confidence. Our analysis corroborates that the editosome has adapted to the structural multiplicity of the mitochondrial mRNA folding space by recognizing a fuzzy continuum of RNA folds that fit a consensus graph descriptor.
高分子质量核糖核蛋白复合物的组装通常依赖于特定 RNA 序列的二元相互作用或精确折叠的 RNA 基序与蛋白质侧的专用 RNA 结合域之间的相互作用。在这里，我们描述了一种由高分子质量蛋白复合物识别 RNA 分子的新分子识别原理。通过化学探测与锥虫生物编辑体结合时线粒体前体 mRNA 的溶剂可及性，我们鉴定了多个类似但不相同的 RNA 基序作为编辑体接触位点。然而，通过将不同的基序视为数学图对象，我们证明它们符合由 4 个顶点 (V) 和 3 个边 (E) 组成的共识 2D 图，拉普拉斯特征值为 0.5477 (λ2)。我们确定合成的 4V(3E)-RNA 足以竞争编辑体前体 mRNA 结合位点，并在体外抑制 RNA 编辑。此外，我们证明仅需要两个拓扑指数就可以高度置信地预测任何 RNA 基序与编辑体的结合。我们的分析证实，编辑体通过识别适合共识图描述符的模糊 RNA 折叠连续体，已经适应了线粒体 mRNA 折叠空间的结构多样性。
